Voiding dysfunction is referred to all the urination actions departing from normal voiding patterns. Voiding dysfunction may happen to anyone of men and women, which include neurogenic bladder developed by neurological abnormality, lower urinary tract symptoms and prostatic hyperplasia by non-neurogenic cause, female urinary diseases represented as urinary incontinence (Korean Continence Society, 2003). It was reported that adults have high prevalence in voiding dysfunction, and that while voiding dysfunction increases with their age, men particularly show linear increase. In lower urinary tract symptoms due to voiding dysfunction, all of men and women are believed to have the highest prevalence of storage phase dysfunction symptoms represented as frequent urination and overactive bladder, and it is reported that they develop in turn voiding phase dysfunction, and symptoms after voiding.
Various voiding dysfunction symptoms such as overactive bladder negatively affect health-related quality of individual life in various aspects, since the quality of individual life cannot help being lowered due to restricted intake of beverages, experience of inconvenience to frequently go to toilet, impact on personal relationship and social life, occurrence of health problems or insufficient sleep at night, and the like (Jeung Im KIM, Young Ho KIM, & Hyun Chul AHN, 2002; Yoo Sik LEE, 2001a).
Overactive bladder syndrome (OAB syndrome) is a composite condition group that has recently established a concept of disease, and referred to represent one or more of conditions such as frequent urination (at least 8 times per day), which frequently urinate by frequently contracting bladder in an abnormal way while urine made in kidneys is filled in the bladder, urgency urination, which is hard to hold urine, and thus has to rapidly go to toilet, urgency incontinence, which on urinating does not sufficiently endure urination and leaks urine to soak wears, and nocturia, which has to urinate one or more times during sleep at night, regardless of being urgency incontinence, provided that there is no urinary tract infection and other clear etiology. Conditions of overactive bladder are related to involuntary contraction to result in state of bladder hyperactivity.
As the bladder consists of smooth muscles and voiding function is regulated by nervous system, various voiding dysfunction may be developed by abnormality of the smooth muscles and the nervous system. It is not still clearly known about main causes of diseases, since overactive bladder is generally developed by a neurogenic cause derived from brain diseases or spinal cord injuries, bladder outlet obstruction represented as male prostatic hyperplasia, weakness of pelvis structure of female, local diseases of urethra and bladder, and the like, but there are many cases caused by aging of detrusor myocytes, obscure dysfunction of detrusor, and the like (Tae Hyung KIM, Journal of Chung Ang University College of Medicine 28(3), p 143-149, 2003).
While the overactive bladder syndromes are not one process of aging, event probability increases with age. Urgency incontinence is more common developed in women, although the ratio of men to women is similar. It is variously reported from 12.7% to 30.5% at home, and in accordance with one research in Europe, the overactive bladder is a common disease such that it is developed in men at 16% and in women at 17%, over age 40, and specifically in men at 42% and in women at 31%, over age 75, and these statistics are also similar to developed countries such as USA and Japan (2011, Korean Continence Society, Guidelines on Overactive Bladder). The overactive bladder showed decrease in quality of life by affecting basic physical activity, sex life, and moreover social activity socially and mentally, and as a result of surveying HRQOL (health-related quality-of-life) for patients, it showed to have higher impact on quality of life than diabetes (Liberman J N, Hunt T L, Stewart W F, Wein A, Zhou Z, Herzog A R, et al. Health-related quality of life among adults with symptoms of overactive bladder: results from a U.S. community-based survey. Urology 2001; 57:1044-50).
Although antimuscarinic drugs are now widely used as an initial standard treatment of the overactive bladder, there is still no report for internationally practiced and controlled clinical trials to certainly demonstrate effectiveness, and it is reported that since these drugs have anticholinergic property affected across nervous system, adverse effects such as thirst, constipation, blurred vision and acute urinary retention are occurred at the rate of 1-2 in 10 people. Such adverse effects are reported as one cause to lower drug compliance in case of patients with voiding dysfunction needed regulated water intake, and for this reason, it is consistently required for development of novel alternative drugs for voiding dysfunction such as overactive bladder (J. Korean Continence Soc 2009; 13:7-22).
Urgency incontinence is for involuntary urine leakage to be suddenly developed after a severe condition of urine urgency, in which its causal factor is known as particular scene, sounds, contact with running water, position change, and the like. Urgency urine is also called urine urgency and referred to a condition that a desire intended to urinate suddenly occurs, and means a state that once one feels a sense for urination, he does not endure urination. In this case, it is known that if one does not immediately urinate, pain may be induced, and severely, the bladder may arbitrarily contact to proceed into urgency incontinence leaking urine. Frequent urination was defined as a case of urinating 8 times or more for 24 hours, unlike normal adults urinating 4˜6 times per day with a voiding volume at a time of about 300 cc, but the definition of frequent urination was extended by defining it by the International Continence Society in 2002 as a case that a patient himself feels to very frequently urinate. Frequent urination is caused by excess water intake, detrusor hyperactivity, bladder capacity decrease, supersensitivity of bladder, and the like to be one of representative conditions of voiding dysfunction referred to abnormal voiding conditions. Nocturnal urine is referred to urinate after waking up during sleep at night, which is classified as nocturnal polyuria that a night voiding volume is relatively high over the daily voiding volume and nocturia that does not. To be defined as nocturnal urine, it should be necessary accompanied by sleep before and after voiding, and the patient with nocturia frequently wakes up and does not fall asleep easily, so that he is sleepy and tired in the daytime due to disturbed sleep to result in inconvenience in his daily life. Furthermore, an elderly person has a problem to increase risk of fall or fracture. Nocturia is reported to be associated with various factors such as age, life habit, polyuria, nocturnal polyuria, bladder disorder, sleep disorder, and psychological factor. Interstitial cystitis is also called bladder pain syndrome or chronic cystitis. There was no characteristic pathologic manifestation such as bacterial infection, and the exact cause was not still found. Although it is known that this develops, as defects occur in bladder epithelial cells to damage bladder mucosal lining between urine and blood flow, inflammation in bladder or vascular disorders of bladder, bladder mucosal damages and psychosomatic disorders may serve as an inducer. While this occurs in all of men and women, the extent of 90% is revealed to female, mostly, in mid-forties. Abnormal sensory urgency urination and frequent urination are developed as symptoms, with chiefly complaining bladder pain. When urine is filled, the symptoms become worse, while those have less pain on voiding. With urinating 1˜2 times or more and an average of 4 times at night, there is less hematuria. With urinating at least 8 times or more and an average of 16 times in the daytime, the normal person has a voiding volume at a time of 250 ml, while the patient suffering from this disease has an average volume of 75 ml. 3 in 4 patients have more severe symptoms due to sex conducts, and menstruation cycles, stress, foods and the like also affect deterioration of symptoms. For treatment, following administration of an antidepressant and anesthesia, an operation such as bladder hydrodistention, cystolysis, bladder enlargement, urinary diversion is implemented or a drug such as an anticholinergic drug or alpha-adrenergic receptor blocker, an antihistaminic drug, a steroid, silver nitrate, heparin is administrated, but the effect of treatment is not high, and thus it is required for novel drugs to treat such voiding dysfunction.
Meanwhile, Piperis Longi Fructus native to India as a fruit of Piperis Longum L. being a climbing woody plant of Piperaceae is cultivated in China and Indonesia to be imported into Korea, which is used under the oriental medicine name of Pilbal at home.
Piper Longum L. contains various components such as essential oils (camphene, piperonal, sabinene, limonene, myrcene), a fatty acid (palmitic acid) and alkaloids (piperidine, piperine, piperannine), has an effect of alleviating pain in hot body as an interior warming medicine warming the spleen and stomach, in the oriental medicine and is referred to be used in dysentery, vomit, abdominal inflation, toothache, analgesia and diarrhea. In India, Ayurveda, Piper Longum L. is currently used under the name of PIPPALI, and referred to have been used as a digestive stimulator, a carminative, an expectorant, a bronchodilator, an anthelmintic, a sedative, a circulation stimulator, an aphrodisiac (Traditional Medicine of India, Shinilbooks, December 2011), and as pharmaceutical actions of Piper Longum L., antibacterial, anticonvulsant, skin vasodilatation, antioxidation, antimyocardial ischemia, antilipidemic, anticancer and antiobestic actions have been reported. However, it is not still known about an effect of improving voiding dysfunction with Piper Longum L.